This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Several observations indicate that CD8+ T cells control virus replication during HIV and SIV infection. However, the mechanisms underlying this antiviral effect are still poorly understood. In a recent study (Klatt, PloS Pathogens 2010), we found that, in both early and late SIV infection, depletion of CD8+ lymphocytes does not change the vivo lifespan of infected cell, thus indicating that SIV suppression mediate by CD8+ lymphocytes may involve direct cytolythic effects as well as non-cytolythic mechanisms. The current project, funded in August 2010, will include experiments of in vivo CD8+ lymphocyte depletion aimed at better elucidating the antiviral effects of these cells during chronic SIV infection of RMs. We are currently in the planning phase of the complex in vivo experiments of CD8 depletion proposed in two of the four Aims of this proposal, in which a total of 15 healthy RM will be first infected with SIVmac and then CD8 depleted during the early stages of chronic infection (I.e. after the viral set point has been reached). A number of key immunological and virological markers will be analyzed by histology, flow cytometry, and virological assays. We recently identified the sufficient number of animals that have been already been placed under quarantine and assigned to the study. As such, we will soon start the proposed experiment, and the relevant results will be analyzed as they are generated. We believe that these experiments will provide important insights into CD8+ lymphocyte inhibition of virus replication during SIV infection.